Fig. 1
From: Torpor induces reversible tau hyperphosphorylation and accumulation in mice expressing human tau
Phospho-tau and total tau levels during different torpor stages in the hippocampus of mtau and htau mice (A) Steady torpor was induced in mice using ambient temperature (Ta) reduction on day 1 (from 21 °C to 19 °C) and food restriction on day 2 (1.5 g from 9AM till 17PM), followed by a fasting period of maximally 40 h. During the second night of fasting, ∼70% of the mice entered torpor [9]. Mice were euthanised during deep torpor (T; ∼10:00, Tb <26 °C for at least 6 h) or directly after arousal (A; ∼16:00, Tb 37 °C for 2 h). Euthermic (EU) control animals were held at normal housing temperature, fed ad lib, and euthanised on the same day ∼13:00. (B) Representative immunoblot images showing AT8 staining (Ser202/Thr205 hyperphosphorylated tau) in hippocampal lysates and gel images showing total protein loading. (C) Representative immunoblot images showing TAU-5 staining (total tau) in hippocampal lysates and gel images showing total protein loading. (D) Quantification indicates that AT8 intensity during torpor was significantly higher in mtau and htau mice compared to euthermic controls (5.63 ± 1.36 and 16.87 ± 4.50 vs. 0.63 ± 0.69 and 1.27 ± 1.70) and 3.0x higher in htau compared to mtau mice (2-way ANOVA, post-hoc Holm-Sidak, F2,42 = 12.67, **** p < 0.0001, *** p < 0.001, ** p < 0.01, * p < 0.05, n.s. p > 0.05; tau-/- EU: n = 7, T: n = 4, A: n = 7; mtau EU/T/A: n = 6; htau EU/T/A: n = 5). (E) Quantification shows that total tau levels do not differ between torpor stages, and that htau mice express ∼3x more total tau than mtau mice (htau EU: 13.67, T: 9.46 and A: 10.79; mtau EU: 3.63, T: 3.36 and A: 3.69; 2-way ANOVA, post-hoc Holm-Sidak, F2,42 = 65.0, **** p < 0.0001, *** p < 0.001, ** p < 0.01, * p < 0.05, n.s. p > 0.05; tau-/- EU: n = 7, T: n = 4, A: n = 7; mtau EU/T/A: n = 6; htau EU/T/A: n = 5). (F) Relative AT8 expression to TAU-5 levels shows similar AT8 levels in mtau and htau mice (htau EU: 0.169, T: 2.318 and A: 0.315; mtau EU: 0.223, T: 2.033 and A: 0.390; 2-way ANOVA, post-hoc Holm-Sidak, n.s. p > 0.05)